Electrophysiologic effects of d-sotalol in humans

Sotalol is a beta-adrenergic blocking agent that prolongs the duration of the cardiac action potential in humans, without affecting the upstroke velocity of depolarization. The dextrorotatory isomer, d-sotalol, retains these class III effects, but has little beta-blocking activity in vitro. d-Sotalol has not been studied extensively in humans. The electrocardiographic (ECG) and electrophysiologic effects of d- and d,l-sotalol were therefore assessed in a prospective randomized study of 20 patients. Each patient received either d-sotalol (1, 1.5 or 2 mg/kg body weight) or d,l-sotalol (1 mg/kg) by intravenous infusion. The QT and QTc intervals were prolonged and refractoriness increased in the atrium, atrioventricular (AV) node, His-Purkinje system and right ventricle after both d- and d,l-sotalol. After d-sotalol, the increases in both QT and QTc intervals and in atrial and ventricular effective refractory periods were dose dependent. Highly significant linear correlation was demonstrated between the plasma sotalol level and the change in QT (r = 0.86, p = 0.001) and QTc intervals (r = 0.79, p = 0.002), and between the plasma sotalol level and the effective refractory period of the right atrium (r = 0.75, p = 0.005) and ventricle (r = 0.70, p = 0.025). This study confirms that d-sotalol has effects consistent with class III properties. It demonstrates these effects in humans, and suggests that d-sotalol may prove to be a useful antiarrhythmic agent.     

Cardiovascular observation unit: meeting the expanding needs of an integrated cardiovascular center.

By developing a flexible unit that can easily manage a diverse cardiac population, the Cardiovascular Center as well as the Medical Center reduced expenses and increased operational efficiency. In addition to the economic and operational benefits, patients and their families have been impacted favorably by the unit's design and operation. As cardiovascular administrators search for ways to reduce expenses and increase operational efficiencies, they should consider the positive effects of a unit similar to our CVOU within their institution.     

Completion pneumonectomy: indications, complications, and results

From 1958 through 1985, a total of 113 consecutive patients had completion pneumonectomy (CP). Indications for pulmonary resection resulting in CP were lung cancer (LC) in 64 patients, pulmonary metastases (PM) in 20, and benign lung disease (BLD) in 29. Operative mortality was 12.4% (14 deaths) but varied according to the indication for CP. Mortality was 9.4% for LC, 0% for PM, and 27.6% for BLD. Forty-three patients (38.1%) had major complications (26 of 64 with LC, 40.6%; 1 of 20 with PM, 5.0%; and 16 of 29 with BLD, 55.2%). Five-year actuarial survival for patients with LC was 26.4% but varied according to stage. Five-year survival for patients with PM was 40.8% and with BLD was 27.2%. We conclude that CP for BLD carries marked operative mortality and morbidity, usually due to intense reaction around hilar structures and concurrent active infection or fistula. In contrast, CP for LC and PM can be performed with low mortality, acceptable morbidity, and gratifying long-term survival.     

Treatment of ventricular arrhythmias

Within the past 20 years, our knowledge concerning the epidemiology, natural history, and treatment of VT has expanded greatly. A variety of effective pharmacologic, surgical and electrical therapies for VT are now available to the clinician. Patients who present with ventricular, tachyarrhythmias should undergo a comprehensive medical evaluation directed at identifying and treating such factors as ischemia, congestive heart failure, valvular heart disease, sensitivity to cardioactive drugs, and metabolic derangements. Many patients who present with asymptomatic ventricular arrhythmias do not require specific antiarrhythmic drug therapy. However, certain patients who have already suffered a life-threatening arrhythmia or who are at high risk for such arrhythmia should be vigorously treated with specific antiarrhythmic therapy guided for that individual patient. The efficacy of any antiarrhythmic treatment should be assessed by ECG monitoring, exercise testing, and/or electrophysiologic study. In the near future, potentially revolutionary new electrical therapies for ventricular tachyarrhythmias will be evaluated. It is to be hoped that these devices used in combination with pharmacologic and surgical therapies may dramatically reduce the incidence of sudden cardiac death in high-risk patients.     

Repellents and other personal protection strategies against Aedes albopictus

Five chemical repellents, a controlled-release repellent formulation, Avon Skin-So-Soft bath oil and permethrin-impregnated clothing fabric were assayed for personal protection against bites of Aedes albopictus. On skin the chemical repellents provided significant (P = 0.05) protection from biting; however, Ae. albopictus was more sensitive to the repellents than the standard, Ae. aegypti. Two experimental repellents provided 6-7 h protection from bites, 25% deet in ethanol provided greater than 8 h protection, a controlled-release formulation containing 35% deet provided greater than 10 h protection, and the Avon product provided 0.64 h protection from bites. Permethrin-treated fabric provided complete protection from mosquito bites through 0-5 washings. Repellent products containing greater than or equal to 12% deet should provide satisfactory protection against Ae. albopictus; the use of permethrin-impregnated clothing should provide additional protection.     

GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing

The beta-amyloid (Abeta) precursor protein (APP) is cleaved sequentially by beta-site of APP-cleaving enzyme (BACE) and gamma-secretase to release the Abeta peptides that accumulate in plaques in Alzheimer's disease (AD). GGA1, a member of the Golgi-localized gamma-ear-containing ARF-binding (GGA) protein family, interacts with BACE and influences its subcellular distribution. We now report that overexpression of GGA1 in cells increased the APP C-terminal fragment resulting from beta-cleavage but surprisingly reduced Abeta. GGA1 confined APP to the Golgi, in which fluorescence resonance energy transfer analyses suggest that the proteins come into close proximity. GGA1 blunted only APP but not notch intracellular domain release. These results suggest that GGA1 prevented APP beta-cleavage products from becoming substrates for gamma-secretase. Direct binding of GGA1 to BACE was not required for these effects, but the integrity of the GAT (GGA1 and TOM) domain of GGA1 was. GGA1 may act as a specific spatial switch influencing APP trafficking and processing, so that APP-GGA1 interactions may have pathophysiological relevance in AD.